Iodine → 2-Chloro-5-fluoro-4-isopropyl-pyrimidine

Temperatur

0 °C

A solution of 5-fluoro-2-chloropyrimidine (5.00 g, 37.7 mmol) in 1,2-dimethoxyethane (25 mL) is treated with a solution of 2 M isopropyl magnesium chloride in tetrahydrofuran (28.3 mL, 56.6 mmol) while keeping the temperature below 15° C. The resulting solution is stirred for one hour under nitrogen and then cooled to 0° C. and treated drop wise with a solution of triethylamine (5.76 mL, 37.7 mmol) in tetrahydrofuran (5 mL). A solution of iodine (9.58 g, 37.7 mmol) in tetrahydrofuran (20 mL) is added. The reaction is quenched with water and saturated sodium bicarbonate and saturated sodium bisulfate are added. The mixture is extracted three times with ethyl acetate. The combined organic layers are dried over sodium sulfate and the solvent is removed under vacuum. The crude product is purified over silica gel with a 30 minute gradient, dichloromethane/hexanes (5 to 100%) to give the title compound (2.55 g, 39%). GC/MS (m/e): 174.

1. customthe temperature below 15° C
2. customThe reaction is quenched with water and saturated sodium bicarbonate and saturated sodium bisulfate
3. additionare added
4. extractionThe mixture is extracted three times with ethyl acetate
5. dry with materialThe combined organic layers are dried over sodium sulfate
6. customthe solvent is removed under vacuum
7. customThe crude product is purified over silica gel with a 30 minute gradient, dichloromethane/hexanes (5 to 100%)

ORD-Eintrag

ord-fb74de0fbbbd48fc942790f823784b9e

Quelldatensatz

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08889856B2